Abstract: :
Purpose:To understand cone photoreceptor survival, which iscritical for the development of therapies for macular degeneration,new experimental approaches are needed. We have studied veryearly changes within the outer nuclear layer (ONL) of the ratduring the first 60 h after light, focusing on rod and conecellular integrity.Methods:After 3 days dark adaptation, albinorats were exposed for 5 h to circular fluorescent bulbs andretinas were sampled at 6-h intervals (0-60 h). Cell count profilesof the ONL were constructed from sections cut from the superiorto the inferior retinal margin through the optic nerve. Photoreceptorcell damage and loss were observed at both the light- and electron-microscopelevel; EM sections were obtained from the region of highestlight sensitivity, centered 33% from the superior margin.Results:Withinthe retinal area of highest damage, cones display marked sensitivityat 6 h after light onset, with swelling around the nucleus,while nuclear disorganization occurs from 12-18 h. This timecourse is unlike that seen in rods. The first indication ofrod damage, peripheral nuclear condensation, occurs around 18h with no evidence of swelling. In regions adjacent to the photodamagedarea, cones appear normal. By 60 h 48% of photoreceptor nucleiare gone; no photoreceptor nuclei remain within the subretinalspace in the area of highest damage.Conclusion:Light damagein cones appears earlier and is morphologically different fromthat observed in rods, suggesting a different mechanism. Countsof damaged cones (10/600 undamaged rods) suggest that theseare green-sensitive cones containing an opsin similar to thatof rods. Therefore, the wavelengths triggering cone degenerationwould be the same as those for rods. Because the rat retinais predominately rod, until now it has been difficult to applywhat is known about cell degeneration to cones of the humanmacula. However, our observations that cones are selectivelyaffected at a very early time suggest that rat retina can beused to understand mechanisms of cone degeneration.